Prediagnostic level of serum retinol in relation to reduced risk of hepatocellular carcinoma.

The Cancer Center, University of Minnesota, Minneapolis, MN, USA.
CancerSpectrum Knowledge Environment (Impact Factor: 14.07). 04/2006; 98(7):482-90. DOI: 10.1093/jnci/djj104
Source: PubMed

ABSTRACT Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses.
We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided.
Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed.
High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.

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    ABSTRACT: (a) Objectives: the development of a simple, rapid, sensitive, and accurate HPLC-UV method for the simultaneous determination of retinol and α-tocopherol in human plasma, suitable for the evaluation of these vitamins in pregnant women suffering from intrahepatic cholestasis of pregnancy (ICP). (b) Design and methods: chromatographic separation of vitamins was achieved with a microcolumn BDS HYPERSIL C18 (100 mm × 2.1 mm, 2.4 μm) using a C18 guard column. The developed and validated HPLC method proposed in this study was applied in the assessment of plasma concentrations of retinol and α-tocopherol in normal pregnancy (n = 37) and in pregnancy complicated with ICP (n = 19). (c) Results: the validation of the method showed excellent linearity for retinol and α-tocopherol (r2: 0.998 and 0.997), high sensitivity (LOD: 0.02 and 0.11 μM, LOQ: 0.07 and 0.36 μM), and high recovery (96.0-104.0% and 99.3-102.0%), respectively. The method requires a low sample volume and all procedures of sample preparation and analytical determination take less than 20 min to be completed. The evaluation of the results in ICP patients showed that α-tocopherol significantly diminished compared to normal pregnant women (13.1 ± 2.9 vs. 22.4 ± 2.2 μM, p < 0.05) whereas retinol remains unchanged (1.27 ± 0.21 vs. 1.25 ± 0.10 μM). (d) Conclusions: a simple, accurate, reliable, selective, highly sensitive and cost effective method suitable for routine determination of retinol and α-tocopherol in biological samples is proposed. It was possible to determine the decrease of α-tocopherol in ICP patients by this method.
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